Revascularization of atherosclerotic renal artery stenosis for chronic heart failure versus acute pulmonary oedema.

AIM: The aim of the study is to determine whether the apparent benefit of revascularization of renal artery stenosis for 'flash' pulmonary oedema extends to heart failure patients without a history of prior acute pulmonary oedema. METHODS: A prospective study of patients with renal artery stenosis and heart failure at a single centre between 1 January 1995 and 31 December 2010. Patients were divided into those with and without previous acute pulmonary oedema/decompensation. Survival analysis compared revascularization versus medical therapy in each group using Cox regression adjusted for age, estimated glomerular filtration rate, blood pressure and co-morbidities. RESULTS: There were 152 patients: 59% male, 36% diabetic, age 70 ± 9 years, estimated glomerular filtration rate 29 ± 17 mL/min per 1.73 m2 ; 52 had experienced previous acute pulmonary oedema (34%), whereas 100 had no previous acute pulmonary oedema (66%). The revascularization rate was 31% in both groups. For heart failure without previous acute pulmonary oedema, the hazard ratio for death after revascularization compared with medical therapy was 0.76 (0.58-0.99, P = 0.04). In heart failure with previous acute pulmonary enema, the hazard ratio was 0.73 (0.44-1.21, P = 0.22). For those without previous acute pulmonary oedema, the hazard ratio for heart failure hospitalization after revascularization compared with medical therapy was 1.00 (0.17-6.05, P = 1.00). In those with previous acute pulmonary oedema, it was 0.51 (0.08-3.30, P = 0.48). CONCLUSION: The benefit of revascularization in heart failure may extend beyond the current indication of acute pulmonary oedema. However, findings derive from an observational study.

Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats.

This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.

beta-Lapachone reduces endotoxin-induced macrophage activation and lung edema and mortality.

beta-Lapachone, a 1,2-naphthoquinone, is a novel chemotherapeutic agent. It has been shown to be capable of suppressing inducible nitric oxide synthase expression and function in rat alveolar macrophages. The authors further performed experiments to examine the molecular mechanism of beta-lapachone on LPS-induced responses in rat alveolar macrophages and to evaluate its in vivo antiinflammatory effect. A significant increase in nitrite production and inducible nitric oxide synthase expression was elicited in macrophages treated with LPS that was inhibited by coincubation with beta-lapachone. beta-Lapachone could also inhibit the production of tumor necrosis factor-alpha induced by LPS. LPS induces protein tyrosine phosphorylation and nuclear factor-kappaB binding activity by gel mobility shift assay in macrophages. These events were significantly inhibited by beta-lapachone. Furthermore, beta-lapachone in vivo protected against the induction of lung edema, lung-inducible nitric oxide synthase protein expression and nuclear factor-kappaB activation, lethality, and increased plasma nitrite and serum tumor necrosis factor-alpha levels induced by LPS. These results indicate that beta-lapachone suppresses inducible nitric oxide synthase induction and tumor necrosis factor-alpha production mediated by the inhibition of protein tyrosine phosphorylation and nuclear factor-kappaB activation caused by LPS. This results in a beneficial effect in an animal model of sepsis.

Effect of dietary treatment with n-propyl gallate or vitamin E on the survival of mice exposed to phosgene.

Phosgene, widely used in industrial processes, can cause life-threatening pulmonary edema and acute lung injury. One mechanism of protection against phosgene-induced lung injury may involve the use of antioxidants. The present study focused on dietary supplementation in mice using n-propyl gallate (nPG)--a gallate acid ester compound used in food preservation--and vitamin E. Five groups of male mice were studied: group 1, control-fed with Purina rodent chow 5002; group 2, fed 0.75% nPG (w/w) in 5002; group 3, fed 1.5% nPG (w/w) in 5002; group 4 fed 1% (w/w) vitamin E in 5002; and group 5, fed 2% (w/w) vitamin E also in 5002. Mice were fed for 23 days. On day 23 mice were exposed to 32 mg m-3 (8 ppm) phosgene for 20 min (640 mg. min m-3) in a whole-body exposure chamber. Survival rates were determined at 12 and 24 h. In mice that died within 12 h, the lungs were removed and lung wet weights, dry weights, wet/dry weight ratios, lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and glutathione (GSH) were assessed. Vitamin E had no positive effect on any outcome measured. There was no significant difference between 1.5% nPG and any parameter measured or survival rate compared with 5002 + phosgene. However, dietary treatment with 0.75% nPG significantly increased survival rate (P

Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid.

All-trans retinoic acid (RA) has proven a major advance in the treatment of acute promyelocytic leukemia (APL). However, the proper management of patients who present with or develop leukocytosis during remission induction with all-trans RA is not established, nor is there a clear relation between leukocytosis and the development of the retinoic acid syndrome. We reviewed the course of our patients who underwent induction with all-trans RA to identify potential factors that might predict for the development of this syndrome and to identify which patients, if any, might specifically benefit from additional treatment with cytotoxic chemotherapy. Seventy-eight courses of all-trans RA therapy were administered to patients with a molecular diagnosis of APL. Initial and peak leukocyte counts, their rate of rise, leukocyte count criteria developed in Europe, and cell surface marker expression were all analyzed relative to subsequent development of both the RA syndrome as well as all causes of early mortality. The outcome of patients who received specific treatment for retinoid-induced leukocytosis was also examined. No factor was found to consistently predict for the development of the RA syndrome. Although the occurrence of the syndrome was positively associated with the peak value of the peripheral blood leukocyte count (P = .001), neither the initial leukocyte count nor the rate of rise in leukocyte counts on days preceding onset of the syndrome were sufficiently well-correlated to be clinically useful (P = .21). The leukocyte count criteria developed in Europe had a sensitivity of 62%, a specificity of 69%, and a positive predictive value that ranged from only 44% to 72%. However, we unexpectedly found that basal expression of CD13 (aminopeptidase N), a cell surface enzyme previously linked to tumor cell invasion and an inferior outcome in patients with acute myeloid leukemia, was highly associated with both development of the syndrome (P < .05) as well as an elevated leukocyte count (P = .006). Neither low-dose chemotherapy nor leukapheresis prevented development of the syndrome nor ameliorated its effects. In fact, 9 of 11 patients who received these interventions sustained fatal or near-fatal events, most of which were due to hemorrhage. However, early treatment with a short-course of high-dose corticosteroids halted progression of the syndrome in most cases. Finally, we found that expression of the type "A" isoform of PML/RAR-alpha (also known as bcr3 or "short") was associated with a significantly shorter duration of relapse-free and overall survival (P = .005).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of hyperbaric oxygen on the rat neurogenic pulmonary edema.

Neurogenic pulmonary edema was induced in rats by bilateral cervical vagotomy. One hour after surgery, 25 animals were placed in an experimental hyperbaric chamber and allowed to breathe oxygen at 1.8 absolute atmospheres for 325 min. Vagotomized controls (N = 25) breathed atmospheric air. Twenty-four h after vagotomy, arterial blood samples were obtained and the lungs removed. Lungs were weighed wet and dry and lung indexes were calculated for each animal by dividing lung wet weight and dry weight by total body weight. There was no statistical difference in total lung weight or total water among groups. However, the dry lung index was about 20% lower in oxygen-treated animals than in controls. There was no difference between hyperbaric oxygen-treated animals and non-vagotomized normal animals, but vagotomized air-breathing controls differed significantly from non-vagotomized animals (P less than 0.05). These results strongly suggest a slower formation of pulmonary edema in the hyperbaric oxygen-treated group.